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1.
Front Pediatr ; 12: 1417265, 2024.
Article in English | MEDLINE | ID: mdl-39156026

ABSTRACT

Background and objective: Despite its acknowledged benefits, the selection of an optimal regional block for analgesia pediatric hernia surgery remains a subject of debate. This study endeavored to conduct a network meta-analysis and systematic review of randomized clinical trials, aiming to amalgamate insights from both direct and indirect comparisons concerning the analgesic effectiveness and safety of various regional blocks post-inguinal hernia repair in children. Method: A comprehensive literature search was performed across PubMed, EMBASE, Web of Science, and the Cochrane Library up to 12 November 2022 by two independent reviewers, employing a standardized protocol. The inclusion criteria encompassed randomized trials focusing on children undergoing inguinal hernia repair utilizing either local infiltration analgesia or regional analgesia. The primary outcomes assessed were pain scores at 2, 6, and 24 h post-operation. Results: The initial search yielded 281 records relating to 1,137 patients. The analysis of ranking probability indicated that Paravertebral Block (PVB) holds the highest likelihood (88% and 48%) of being the most effective in alleviating pain at 2 h and 6 h post-surgery. Trans vs. Abdominis Plane Block (TAPB) emerged as the superior choice for mitigating pain (83%) and decreasing morphine consumption (93%) at 24 h following the operation. Local Anesthetic Infiltration (LAI) was identified as the most effective in shortening the hospital stay, with a 90% probability. Conclusions: Regional anesthesia significantly enhances postoperative pain management in pediatric inguinal hernia repair surgery. For short-term postoperative pain relief, PVB emerges as the most effective technique. Meanwhile, TAPB provides more prolonged analgesia. Although TAPB does not exhibit a pronounced advantage in short-term analgesia, its simplicity and the absence of a need for a special position render it a viable option. However, the interpretation of these results should be approached with caution due to the presence of limited data and heterogeneity. Systematic Review Registration: PROSPERO (CRD42022376435; www.crd.york.ac.uk/prospero).

2.
Angew Chem Int Ed Engl ; : e202413680, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39143747

ABSTRACT

Deep-ultraviolet (UV) birefringent materials are urgently needed to facilitate light polarization in deep-UV lithography. Maximizing anisotropy by regulating the alignment of functional modules is essential for improving the linear optical performance of birefringent materials. In this work, we proposed a strategy to design deep-UV birefringent materials that achieve functional module ordering via weak interactions. Following this strategy, four compounds CN4H7SO3CF3, CN4H7SO3CH3, C(NH2)3SO3CH3, and C(NH2)3SO3CF3 were identified as high-performance candidates for deep-UV birefringent materials. The millimeter-sized crystals of CN4H7SO3CF3, CN4H7SO3CH3, and C(NH2)3SO3CH3 were grown, and the transmittance spectra show that their cutoff edges are below 200 nm. CN4H7SO3CF3 exhibits the largest birefringence (0.149 @ 546 nm, 0.395 @ 200 nm) in the deep-UV region among reported sulfates and sulfate derivatives. It reveals that the hydrogen bond can modulate the module ordering of the heteroleptic tetrahedra and planar π-conjugated cations, thus greatly enhancing the birefringence. Our study not only discovers new deep-UV birefringent materials but also provides an upgraded strategy for optimizing optical anisotropy to achieve efficient birefringence.

3.
Inorg Chem ; 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39167696

ABSTRACT

Borates, due to their structural chemistry diversity and exceptional performance, are premier material systems for investigating UV optical crystals. The B-O anionic groups with high polymerization (B ≥ 6) are much less in the borate-based system, which is worthy of further research. Herein, cations with different radii and proportions are introduced to borate system, and two new highly polymerized borates, LiNa2Ca8B12O24F6Cl (LNCBFC) and Li1.2Na2.8B6O11 (LNBO) were designed and synthesized successfully. LNCBFC possesses commonly isolated high-symmetry [B12O24] groups, while the structure of LNBO contains an unprecedented 1∞[B12O22] chain constructed by [B12O24] groups. Owing to the orientation of the functional motifs in the chain structure, LNBO displays an enhanced birefringence, which is about 25 × higher than that of LNCBFC and retains a short UV cutoff edge (< 200 nm). Even more significantly, a discussion of the cationic modulation of [B12O24]-based compounds and the patterns of isolated [BnO2n] motifs consisting of B-O rings was carried out by reviewing previous studies and existing borates. This work puts forward a decent structure design and property regulation strategy for highly polymerized borates.

4.
Heliyon ; 10(13): e33468, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027576

ABSTRACT

Considering the long-term memory and volatility clustering of the European Union (EU) Carbon Emission Allowances (EUA) futures returns, based on the economy-energy-environment system perspective and the assumption of investors' heterogeneity, this study proposes a joint modeling approach combining the fractionally integrated generalized autoregressive conditional heteroscedasticity model (FIGARCH) and the stochastic cusp catastrophe model (SCC) to examine the equilibrium bifurcations and extreme risks in the EU carbon futures market. The relevant results are threefold. (1) The SCC model has good fitting effect and interpretability, and is an effective method for investigating catastrophe reactions under time-varying volatility conditions. (2) In the EUA futures market, chartists are mainly affected by short-term price and trading volume changes, which leads to the emergence of equilibrium bifurcations, while fundamentalists make investment decisions based on the economy, the energy market, and market supply-demand, which affects the asymmetry of equilibrium bifurcations. (3) Using the catastrophe criterion (i.e., Cardan's discriminant of the equilibrium surface equation), we identify148 equilibrium bifurcation time points in the EUA futures market from December 3, 2009 to September 16, 2020, most of which are concentrated in two upward periods with an average scale of extreme risks is about 32.51 %. Our analysis provides theoretical support for regulatory authorities to stabilize the carbon futures market and build a collaborative extreme risk management framework covering energy and macroeconomics, also proposing suggestions for traders to effectively prevent extreme risks.

6.
Sci Rep ; 14(1): 16131, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997304

ABSTRACT

Rockburst present substantial hazards in both deep underground construction and shallow depths, underscoring the critical need for accurate prediction methods. This study addressed this need by collecting and analyzing 69 real datasets of rockburst occurring within a 500 m burial depth, which posed challenges due to the dataset's multi-categorized, unbalanced, and small nature. Through a rigorous comparison and screening process involving 11 machine learning algorithms and optimization with KMeansSMOKE oversampling, the Random Forest algorithm emerged as the most optimal choice. Efficient adjustment of hyper parameter was achieved using the Optuna framework. The resulting KMSORF model, which integrates KMeansSMOKE, Optuna, and Random Forest, demonstrated superior performance compared to mainstream models such as Gradient Boosting (GB), Extreme Gradient Boosting (XBG), and Extra Trees (ET). Application of the model in a tungsten mine and tunnel project showcased its ability to accurately forecast rockburst levels, thereby providing valuable insights for risk management in underground construction. Overall, this study contributes to the advancement of safety measures in underground construction by offering an effective predictive model for rockburst occurrences.

7.
Materials (Basel) ; 17(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38998200

ABSTRACT

In this study, the SiBCN-Ti series ceramics with different Ti contents were fabricated, and the oxidation resistance and microstructural evolution of the ceramics at 1500 °C for different times were explored. The results show that with the increase in oxidation time, pores and bubbles are gradually formed in the oxide layer. When the oxidation time is less than or more than 4 h, the Ti(C, N) in the ceramics will maintain its initial structure or mostly transform to TiN. The introduction of Ti content can promote the formation of rutile silicate glass, thus healing the cracks and improving the oxidation resistance of the ceramics effectively.

8.
ACS Appl Mater Interfaces ; 16(28): 36658-36666, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38976617

ABSTRACT

Modern crystal structure prediction methods based on structure generation algorithms and first-principles calculations play important roles in the design of new materials. However, the cost of these methods is very expensive because their success mostly relies on the efficient sampling of structures and the accurate evaluation of energies for those sampled structures. Herein, we develop a Machine-learning-Assisted CRYStalline Materials sAmpling sysTem (MAXMAT) aiming to accelerate the prediction of new crystal structures. For a given chemical composition, MAXMAT can generate efficient crystal structures with the help of a Python package for crystal structure generation (PyXtal) and can quickly evaluate the energies of these generated structures using a well-developed machine learning interaction potential model (M3GNET). We have used MAXMAT to perform crystal structure searches for three different chemical systems (TiO2, MgAl2O4, and BaBOF3) to test its accuracy and efficiency. Furthermore, we apply MAXMAT to predict new nonlinear optical materials, suggesting several thermodynamically synthesizable structures with high performance in LiZnGaS3 and CaBOF3 systems.

9.
J Mol Model ; 30(8): 264, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995407

ABSTRACT

CONTEXT: Accurately predicting plasma protein binding rate (PPBR) and oral bioavailability (OBA) helps to better reveal the absorption and distribution of drugs in the human body and subsequent drug design. Although machine learning models have achieved good results in prediction accuracy, they often suffer from insufficient accuracy when dealing with data with irregular topological structures. METHODS: In view of this, this study proposes a pharmacokinetic parameter prediction framework based on graph convolutional networks (GCN), which predicts the PPBR and OBA of small molecule drugs. In the framework, GCN is first used to extract spatial feature information on the topological structure of drug molecules, in order to better learn node features and association information between nodes. Then, based on the principle of drug similarity, this study calculates the similarity between small molecule drugs, selects different thresholds to construct datasets, and establishes a prediction model centered on the GCN algorithm. The experimental results show that compared with traditional machine learning prediction models, the prediction model constructed based on the GCN method performs best on PPBR and OBA datasets with an inter-molecular similarity threshold of 0.25, with MAE of 0.155 and 0.167, respectively. In addition, in order to further improve the accuracy of the prediction model, GCN is combined with other algorithms. Compared to using a single GCN method, the distribution of the predicted values obtained by the combined model is highly consistent with the true values. In summary, this work provides a new method for improving the rate of early drug screening in the future.


Subject(s)
Machine Learning , Humans , Algorithms , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/metabolism , Neural Networks, Computer , Biological Availability , Protein Binding , Small Molecule Libraries/pharmacokinetics , Small Molecule Libraries/chemistry , Pharmacokinetics , Blood Proteins/metabolism
10.
Biomed Eng Online ; 23(1): 53, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858706

ABSTRACT

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.


Subject(s)
Folic Acid , Magnetic Resonance Imaging , Nanocomposites , Neoplasm Metastasis , Stomach Neoplasms , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Animals , Nanocomposites/chemistry , Mice , Cell Line, Tumor , Humans , Folic Acid/chemistry , Manganese Compounds/chemistry , Optical Imaging , Mice, Nude , Oxides
11.
Chem Commun (Camb) ; 60(51): 6516-6519, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38836308

ABSTRACT

The first chloroaluminoborate, CsAlB3O6Cl, with innovative AlO3Cl tetrahedra and a perfect planar arrangement of [B3O6] groups, was structurally designed and synthesized via chlorination of [AlO4] tetrahedra. Simultaneously, the smooth introduction of the [AlO3Cl] group into borates initiates the development of a chloroaluminoborate and greatly enriches the structural chemistry of aluminoborates.

12.
Front Cardiovasc Med ; 11: 1280734, 2024.
Article in English | MEDLINE | ID: mdl-38836066

ABSTRACT

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is linked to an elevated risk of adverse cardiovascular events. Although modern medicine has made significant strides in researching CMVD, we still lack a comprehensive understanding of its pathophysiological mechanisms due to its complex and somewhat cryptic etiology. This greatly impedes the clinical diagnosis and treatment of CMVD. The primary pathological mechanisms of CMVD are structural abnormalities and/or dysfunction of coronary microvascular endothelial cells. The development of CMVD may also involve a variety of inflammatory factors through the endothelial cell injury pathway. This paper first reviews the correlation between the inflammatory response and CMVD, then summarizes the possible mechanisms of inflammatory response in CMVD, and finally categorizes the drugs used to treat CMVD based on their effect on the inflammatory response. We hope that this paper draws attention to CMVD and provides novel ideas for potential therapeutic strategies based on the inflammatory response.

13.
J Nanobiotechnology ; 22(1): 374, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926723

ABSTRACT

BACKGROUND: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. RESULTS: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn2+-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. CONCLUSIONS: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.


Subject(s)
Drug Resistance, Neoplasm , Photothermal Therapy , Animals , Mice , Drug Resistance, Neoplasm/drug effects , Cell Line, Tumor , Humans , Photothermal Therapy/methods , Mice, Inbred BALB C , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Tumor Microenvironment/drug effects , Mice, Nude , Prodrugs/pharmacology , Prodrugs/chemistry , Tumor Hypoxia/drug effects , Manganese/chemistry , Female , Neoplasms/drug therapy , Anthraquinones
14.
J Immunol ; 213(3): 268-282, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38856585

ABSTRACT

Recruitment of immune cells to the injury site plays a pivotal role in the pathology of radiation-associated diseases. In this study, we investigated the impact of the chemokine CCL22 released from alveolar type II epithelial (AT2) cells after irradiation on the recruitment and functional changes of dendritic cells (DCs) in the development of radiation-induced lung injury (RILI). By examining changes in CCL22 protein levels in lung tissue of C57BL/6N mice with RILI, we discovered that ionizing radiation increased CCL22 expression in irradiated alveolar AT2 cells, as did MLE-12 cells after irradiation. A transwell migration assay revealed that CCL22 promoted the migration of CCR4-positive DCs to the injury site, which explained the migration of pulmonary CCR4-positive DCs in RILI mice in vivo. Coculture experiments demonstrated that, consistent with the response of regulatory T cells in the lung tissue of RILI mice, exogenous CCL22-induced DCs promoted regulatory T cell proliferation. Mechanistically, we demonstrated that Dectin2 and Nr4a2 are key targets in the CCL22 signaling pathway, which was confirmed in pulmonary DCs of RILI mice. As a result, CCL22 upregulated the expression of PD-L1, IL-6, and IL-10 in DCs. Consequently, we identified a mechanism in which CCL22 induced DC tolerance through the CCR4-Dectin2-PLC-γ2-NFATC2-Nr4a2-PD-L1 pathway. Collectively, these findings demonstrated that ionizing radiation stimulates the expression of CCL22 in AT2 cells to recruit DCs to the injury site and further polarizes them into a tolerant subgroup of CCL22 DCs to regulate lung immunity, ultimately providing potential therapeutic targets for DC-mediated RILI.


Subject(s)
B7-H1 Antigen , Chemokine CCL22 , Dendritic Cells , Lung Injury , Mice, Inbred C57BL , NFATC Transcription Factors , Receptors, CCR4 , Signal Transduction , Animals , Mice , Dendritic Cells/immunology , Signal Transduction/immunology , Lung Injury/immunology , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/immunology , B7-H1 Antigen/immunology , Immune Tolerance , Alveolar Epithelial Cells/immunology , Alveolar Epithelial Cells/metabolism , T-Lymphocytes, Regulatory/immunology
15.
Front Cardiovasc Med ; 11: 1369642, 2024.
Article in English | MEDLINE | ID: mdl-38716483

ABSTRACT

Refractory heart failure (RHF), or end-stage heart failure, has a poor prognosis and high case fatality rate, making it one of the therapeutic difficulties in the cardiovascular field. Despite the continuous abundance of methods and means for treating RHF in modern medicine, it still cannot meet the clinical needs of patients with RHF. How to further reduce the mortality rate and readmission rate of patients with RHF and improve their quality of life is still a difficult point in current research. In China, traditional Chinese medicine (TCM) has been widely used and has accumulated rich experience in the treatment of RHF due to its unique efficacy and safety advantages. Based on this, we comprehensively summarized and analyzed the clinical evidence and mechanism of action of TCM in the treatment of RHF and proposed urgent scientific issues and future research strategies for the treatment of RHF with TCM, to provide reference for the treatment of RHF.

16.
Chem Sci ; 15(17): 6577-6582, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38699258

ABSTRACT

Infrared (IR) nonlinear optical (NLO) materials with strong NLO response, wide band gap and high laser-induced damage threshold (LIDT) are highly expected in current laser technologies. Herein, by introducing double alkaline-earth metal (AEM) atoms, three wide band gap selenide IR NLO materials AIIMg6Ga6Se16 (AII = Ca, Sr, Ba) with excellent linear and NLO optical properties have been rationally designed and fabricated. AIIMg6Ga6Se16 (AII = Ca, Sr, Ba) are composed of unique [AIISe6] triangular prisms, [MgSe6] octahedra and [GaSe4] tetrahedra. The introduction of double AEMs effectively broadens the band gaps of selenide-based IR NLO materials. Among them, CaMg6Ga6Se16, achieving the best balance between the second-harmonic generation response (∼1.5 × AgGaS2), wide band gap (2.71 eV), high LIDT (∼9 × AgGaS2), and moderate birefringence of 0.052 @ 1064 nm, is a promising NLO candidate for high power IR laser. Theoretical calculations indicate that the NLO responses and band gaps among the three compounds are mainly determined by the NLO-active [GaSe4] units. The results enrich the chemical diversity of chalcogenides, and give some insight into the design of new functional materials based on the rare [AIISe6] prismatic units.

17.
Transl Oncol ; 45: 101973, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38705052

ABSTRACT

OBJECTIVE: High-grade glioma (HGG) patients frequently encounter treatment resistance and relapse, despite numerous interventions seeking enhanced survival outcomes yielding limited success. Consequently, this study, rooted in our prior research, aimed to ascertain whether leveraging circadian rhythm phase attributes could optimize radiotherapy results. METHODS: In this retrospective analysis, we meticulously selected 121 HGG cases with synchronized rhythms through Cosinor analysis. Post-surgery, all subjects underwent standard radiotherapy alongside Temozolomide chemotherapy. Random allocation ensued, dividing patients into morning (N = 69) and afternoon (N = 52) radiotherapy cohorts, enabling a comparison of survival and toxicity disparities. RESULTS: The afternoon radiotherapy group exhibited improved overall survival (OS) and progression-free survival (PFS) relative to the morning cohort. Notably, median OS extended to 25.6 months versus 18.5 months, with P = 0.014, with median PFS at 20.6 months versus 13.3 months, with P = 0.022, post-standardized radiotherapy. Additionally, lymphocyte expression levels in the afternoon radiation group 32.90(26.10, 39.10) significantly exceeded those in the morning group 31.30(26.50, 39.20), with P = 0.032. CONCLUSIONS: This study underscores the markedly prolonged average survival within the afternoon radiotherapy group. Moreover, lymphocyte proportion demonstrated a notable elevation in the afternoon group. Timely and strategic adjustments of therapeutic interventions show the potential to improve therapeutic efficacy, while maintaining vigilant systemic immune surveillance. A comprehensive grasp of physiological rhythms governing both the human body and tumor microenvironment can refine treatment efficacy, concurrently curtailing immune-related damage-a crucial facet of precision medicine.

18.
Biomed Pharmacother ; 176: 116761, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38788596

ABSTRACT

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.


Subject(s)
Cardiovascular Diseases , Ferroptosis , Ferroptosis/physiology , Humans , Animals , Cardiovascular Diseases/metabolism , Lipid Peroxidation , Iron/metabolism
19.
J Ethnopharmacol ; 330: 118264, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38692417

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Optimized New Shengmai Powder (ONSMP) is a sophisticated traditional Chinese medicinal formula renowned for bolstering vital energy, optimizing blood circulation, and mitigating fluid retention. After years of clinical application, ONSMP has shown a significant impact in improving myocardial injury and cardiac function and has a positive effect on treating heart failure. However, many unknowns exist about the molecular biological mechanisms of how ONSMP exerts its therapeutic effects, which require further research and exploration. AIM OF THE STUDY: Exploring the potential molecular biological mechanisms by which ONSMP ameliorates cardiomyocyte apoptosis and ferroptosis in ischemic heart failure (IHF). MATERIALS AND METHODS: First, we constructed a rat model of IHF by inducing acute myocardial infarction through surgery and using echocardiography, organ coefficients, markers of heart failure, antioxidant markers, and histopathological examination to assess the effects of ONSMP on cardiomyocyte apoptosis and ferroptosis in IHF rats. Next, we used bioinformatics analysis techniques to analyze the active components, signaling pathways, and core targets of ONSMP and calculated the interactions between core targets and corresponding elements. Finally, we detected the positive expression of apoptosis and ferroptosis markers and core indicators of signaling pathways by immunohistochemistry; detected the mean fluorescence intensity of core indicators of signaling pathways by immunofluorescence; detected the protein expression of signaling pathways and downstream effector molecules by western blotting; and detected the mRNA levels of p53 and downstream effector molecules by quantitative polymerase chain reaction. RESULTS: ONSMP can activate the Ser83 site of ASK by promoting the phosphorylation of the PI3K/AKT axis, thereby inhibiting the MKK3/6-p38 axis and the MKK4/7-JNK axis signaling to reduce p53 expression, and can also directly target and inhibit the activity of p53, ultimately inhibiting p53-mediated mRNA and protein increases in PUMA, SAT1, PIG3, and TFR1, as well as mRNA and protein decreases in SLC7A11, thereby inhibiting cardiomyocyte apoptosis and ferroptosis, effectively improving cardiac function and ventricular remodeling in IHF rat models. CONCLUSION: ONSMP can inhibit cardiomyocyte apoptosis and ferroptosis through the PI3K/AKT/p53 signaling pathway, delaying the development of IHF.


Subject(s)
Apoptosis , Drugs, Chinese Herbal , Ferroptosis , Heart Failure , Myocytes, Cardiac , Signal Transduction , Animals , Male , Rats , Apoptosis/drug effects , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Ferroptosis/drug effects , Heart Failure/drug therapy , Myocardial Ischemia/drug therapy , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Phosphatidylinositol 3-Kinase/metabolism , Powders , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics
20.
Animals (Basel) ; 14(7)2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38612245

ABSTRACT

Chronic heat stress can have detrimental effects on the survival of fish. This study aimed to investigate the impact of prolonged high temperatures on the growth, antioxidant capacity, apoptosis, and transcriptome analysis of Hong Kong catfish (Clarias fuscus). By analyzing the morphological statistics of C. fuscus subjected to chronic high-temperature stress for 30, 60, and 90 days, it was observed that the growth of C. fuscus was inhibited compared to the control group. The experimental group showed a significant decrease in body weight and body length compared to the control group after 60 and 90 days of high-temperature stress (p < 0.05, p < 0.01). A biochemical analysis revealed significant alterations in the activities of three antioxidant enzymes superoxide dismutase activity (SOD); catalase activity (CAT); glutathione peroxidase activity (GPx), the malondialdehyde content (MDA), and the concentrations of serum alkaline phosphatase (ALP); Aspartate aminotransferase (AST); and alanine transaminase (ALT) in the liver. TUNEL staining indicated stronger apoptotic signals in the high-temperature-stress group compared to the control group, suggesting that chronic high-temperature-induced oxidative stress, leading to liver tissue injury and apoptosis. Transcriptome analysis identified a total of 1330 DEGs, with 835 genes being upregulated and 495 genes being downregulated compared to the control group. These genes may be associated with oxidative stress, apoptosis, and immune response. The findings elucidate the growth changes in C. fuscus under chronic high temperature and provide insights into the underlying response mechanisms to a high-temperature environment.

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